Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy.
OBJECTIVE
Plaque with dense inflammatory cells, including macrophages, thin fibrous cap and superficial necrotic/lipid core is thought to be prone-to-rupture. We report a time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) technique for detection of such markers of plaque vulnerability in human plaques.


METHODS
The autofluorescence of carotid plaques (65 endarterectomy patients) induced by a pulsed laser (337 nm, 0.7 ns) was measured from 831 distinct areas. The emission was resolved spectrally (360-550 nm range) and temporally (0.3 ns resolution) using a prototype fiber-optic TR-LIFS apparatus. Lesions were evaluated microscopically and quantified as to the % of different components (fibrous cap, necrotic core, inflammatory cells, foam cells, mature and degraded collagen, elastic fibers, calcification, and smooth muscle cell of the vessel wall).


RESULTS
We determined that the spectral intensities and time-dependent parameters at discrete emission wavelengths (1) allow for discrimination (sensitivity >81%, specificity >94%) of various compositional and pathological features associated with plaque vulnerability including infiltration of macrophages into intima and necrotic/lipid core under a thin fibrous cap, and (2) show a linear correlation with plaque biochemical content: elastin (P<0.008), collagen (P<0.02), inflammatory cells (P<0.003), necrosis (P<0.004).


CONCLUSIONS
Our results demonstrate the feasibility of TR-LIFS as a method for the identification of markers of plaque vulnerability. Current findings enable future development of TR-LIFS-based clinical devices for rapid investigation of atherosclerotic plaques and detection of those at high-risk.
Marcu
Laura
L
University of California Davis, Department of Biomedical Engineering, Davis, CA 95616, USA. lmarcu@ucdavis.edu
Jo
Javier A
JA
Fang
Qiyin
Q
Papaioannou
Thanassis
T
Reil
Todd
T
Qiao
Jian-Hua
JH
Baker
J Dennis
JD
Freischlag
Julie A
JA
Fishbein
Michael C
MC
D002114:Calcinosis / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017536:Carotid Artery, Common / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D016894:Endarterectomy, Carotid; D005240:Feasibility Studies; D005336:Fiber Optic Technology; D005355:Fibrosis; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D007834:Lasers; D008055:Lipids / Q000032:analysis; D009336:Necrosis; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012421:Rupture; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013997:Time Factors
D008055:Lipids; D003094:Collagen; D004549:Elastin